Undifferentiated B-cell lymphomas occur predominantly in children and young adults in a) a geographically delineated form, which is EBV associated, b) a sporadic, widespread form which is not EBV associated, and c) a form arising in certain immunodeficiency syndromes notably that occurring predominantly in homosexual drug abusers, which is also EBV associated. The goals of the present work are to gain information on the epidemiology, pathogenesis and biological differences among the several forms of undifferentiated lymphoma. Links have been established with a number of cancer centers in various parts of the world as part of a concerted effort to characterize, with more precision than has hitherto been achieved, differences in the spectrum of lymphoid neoplasia that occurs in different environments. Biological studies are carried out on cell lines derived from all three of the above categories of undifferentiated lymphomas. Of particular interest is the expression of genes involved in specific chromosomal translocations associated with these tumors, namely the immunoglobulin genes and c-myc oncogene, and changes in the expression of these genes during differentiation of the cell lines. Phorbol esters induce plasma-cytoid differentiation, characterized by ultrastructural and immunological changes, in most of the cell lines. Such studies may provide information as to whether c-myc transcription is influenced by promotor or enhancer sequences normally concerned with immunoglobulin gene regulation. A study of the differential expression of surface antigens in different phases of the cell cycle and in different growth phases has been carried out to determine whether antigen expression is altered in cells which are not rapidly proliferating, e.g., by virtue of poor nutrient supply, and to begin to comprehend what factors govern surface antigen expression and how surface antigen density is maintained during of cell doubling. The differences between African and American Burkitt's lymphoma are being further characterized. The B2 antigen, for example, present in activated lymphocytes is expressed by African rather than American cell lines. A detailed analysis of differences in complement receptors has been completed.